Diffusion of drugs enclosed in polymer matrices is important in many biomedical and biochemical applications. The term "drug" as used herein refers to any substance having pharmaceutical activity in a subject.
Following implantation of such matrices, and due to the difference in the concentration gradient of the amount of drug in the matrix relative to the amount of drug in the surrounding tissues, there is a driving force for the drug to leave the matrix by diffusion.
When the mesh size or "pore" size in a matrix, which is the distance between neighboring polymer chains in the matrix, is smaller than the size of the diffusing drug, the release rate of the drug is decreased because there is an increase in diffusion hindrance. Flexible polymers can fill space more effectively than rigid polymers when concentrated. Thus, it is usually possible to obtain much smaller mesh sizes with flexible polymers than when using rigid polymers.
However, diffusion hindrance increases in relation to increased flexibility of the polymer used in the matrix (Johansson et al, Macromolecules, 24: 6019 (1991)). That is, polymers which are more rigid generally reduce diffusion rates more effectively than flexible polymers having the same mesh size. The reason for this difference is thought to be that the primary resistance to diffusion in flexible polymer matrices is frictional. Flexible polymer chains can distort, and thus allow the drug to more readily diffuse out of the matrix (Phillies, J. Phys. Chem., 93: 5029 (1989)). In contrast, rigid polymer chains act as immovable obstacles, and cause the diffusing drug to take a tortuous and much more restricted path in leaving the matrix (Doi et al, Chapter 9, The Theory of Polymer Dynamics, Clarendon Press, Oxford (1986)). However, due to the molecule's rigidity, one cannot obtain the smaller mesh sizes with a rigid polymer which can be achieved using a flexible polymer.